The Fate of Global Precedence With Age

The literature is virtually devoid of studies examining the effect of aging on the ''global precedence'' effect (Navon, D. [1977]. Cognitive Psychology, 9, 353-383). In this paradigm, global letters formed with local letters are shown, and the subject has to recognize either the local or the global letters. The relation between the global and the local letters is either congruent, neutral, or conflicting. Five experiments are reported, with five sets of 16 young and five sets of 16 elderly, healthy, adult subjects. The global precedence effect was observed in both age groups in the basic perceptual experiment as designed by Navon (Experiment 1). In addition, young and elderly subjects were able to process separately the global and the local shapes when attention was not directed towards a specific level (Experiment 1a). However, subpopulations emerged, especially in the elderly, depending on their ability to ''resist'' to the interference of the global shape upon the processing of the local form. This could support the few indirect published data suggesting that global precedence tends to diminish or to disappear with age. In experiments 2 and 2a, subjects were retained only if they did process the local level better than at random. Global precedence was confirmed in both young and elderly subjects. Again, elderly subjects manifested an increased sensitivity to interference. Moreover, a general effect of age remained, even in the control (neutral) conditions, suggesting difficulties of encoding in elderly. Therefore, in Experiment 3, encoding conditions of both age groups were equated by increasing exposure durationof the material for elderly. Subjects of Experiment 3 were also submitted to a Strooptest, to verify whether the increased sensitivity to interference in the elderly was specific to the ''Navon task'' or the expression of a general effect of aging on inhibition mechanisms. The global precedence phenomen on was observed in young andelderly subjects, with no sign of an effect of age under these conditions; in elderly, furthermore, the interference effect did not appear to result froma general aspecific deficit of inhibition mechanisms. It thus appears that the global precedence phenomenon resists well the effects of aging, but that subpopulations of elderly subjects should be considered in future studies.     

Reduced plasticity and mild cognitive impairment-like deficits after entorhinal lesions in hAPP/APOE4 mice

Mild cognitive impairment (MCI) is a clinical condition that often precedes Alzheimer disease (AD). Compared with apolipoprotein E-ε3 (APOE3), the apolipoprotein E-ε4 (APOE4) allele is associated with an increased risk of developing MCI and spatial navigation impairments. In MCI, the entorhinal cortex (EC), which is the main innervation source of the dentate gyrus, displays partial neuronal loss. We show that bilateral partial EC lesions lead to marked spatial memory deficits and reduced synaptic density in the dentate gyrus of APOE4 mice compared with APOE3 mice. Genotype and lesion status did not affect the performance in non-navigational tasks. Thus, partial EC lesions in APOE4 mice were sufficient to induce severe spatial memory impairments and synaptic loss in the dentate gyrus. In addition, lesioned APOE4 mice showed no evidence of reactional increase in cholinergic terminals density as opposed to APOE3 mice, suggesting that APOE4 interferes with the ability of the cholinergic system to respond to EC input loss. These findings provide a possible mechanism underlying the aggravating effect of APOE4 on the cognitive outcome of MCI patients.     

IL-9 and its Receptor: From Signal Transduction to Tumorigenesis

IL-9 is a multifunctional cytokine secreted by TH2 lymphocytes. Besides its role during immune responses, its growth factor and antiapoptotic activities on multiple transformed cells suggest a potential role in tumorigenesis. Indeed, IL-9 overexpression induces thymic lymphomas in mice, and IL-9 production is associated with Hodgkin disease and HTLV-I transformed T cells in humans. IL-9 activities are mediated by a specific receptor chain that forms a heterodimeric receptor with the common gamma chain also involved in IL-2,4,7,15 and 21 signaling. The IL-9 receptor and common gamma chains associate with JAK1 and JAK3, respectively and trigger the STAT-1, -3 and -5, IRS and RAS-MAPK pathways. Moreover, in vitro, dysregulated IL-9 response can lead to autonomous cell growth and malignant transformation of lymphoid cells associated with constitutive activation of the Jak/STAT pathway.     

Type-I Interferon assessment in 45 minutes using the FilmArray® PCR platform in SARS-CoV-2 and other viral infections

Low concentrations of type-I interferon (IFN) in blood seem to be associated with more severe forms of Coronavirus disease 2019 (COVID-19). However, following the type-I interferon response (IR) in early stage disease is a major challenge. We evaluated detection of a molecular interferon signature on a FilmArray® system, which includes PCR assays for four interferon stimulated genes. We analyzed three types of patient populations: (i) children admitted to a pediatric emergency unit for fever and suspected infection, (ii) ICU-admitted patients with severe COVID-19, and (iii) healthcare workers with mild COVID-19. The results were compared to the reference tools, that is, molecular signature assessed with Nanostring® and IFN-α2 quantification by SIMOA® (Single MOlecule Array). A strong correlation was observed between the IR measured by the FilmArray®, Nanostring®, and SIMOA® platforms (r-Spearman 0.996 and 0.838, respectively). The FilmArray® panel could be used in the COVID-19 pandemic to evaluate the IR in 45-min with 2 min hand-on-time at hospitalization and to monitor the IR in future clinical trials.     

Effect of build orientation on the manufacturing process and the properties of stereolithographic dental ceramics for crown frameworks

Statement of problemStereolithography (SLA) ceramic crown frameworks are suitable for clinical use, but the impact of SLA build orientation has not been identified.PurposeThe purpose of this in vitro study was to investigate the effect of 3 build orientations on the physical and mechanical properties and the microstructure of SLA alumina dental ceramics.Material and methodsThe physical and mechanical properties and microstructures of 3 different oriented SLA alumina ceramics (ZX, ZY, and XY) were evaluated by visual observation, hydrostatic weighing (n=10/group), Weibull analyses (n=30/group), scanning electron microscopy, 3-point flexural strength (n=30/group), fracture toughness (indentation, single-edge-V-notched-beam) (n=4/group), and Vickers hardness (n=15/group) testing. The hydrostatic weighing, 3-point flexural strength, fracture toughness, and Vickers hardness testing data were statistically analyzed (α=.05).ResultsThe minimum resting period of slurries between the polymerization of 2 layers was shorter for the ZY- and ZX-oriented specimens and increased with the layer surface. The density and Vickers hardness of the SLA-manufactured specimens were similar for all groups (P>.05). The 95% confidence intervals of the Weibull moduli of the ZX- and ZY-oriented specimens were higher than that of the XY-oriented specimens, with no overlap fraction. The ZY-oriented specimens displayed significantly higher 3-point flexural strength (P<.05) and fracture toughness as evaluated by the single-edge-V-notched-beam method than the ZX-oriented specimens (P<.05). They also displayed significantly higher 3-point flexural strength than the XY-oriented specimens (P<.05). The microstructural analysis showed that the texturing was heterogeneous and that the major axis of the large grains of alumina ran parallel to the orientation of the layers.ConclusionsThe ZY orientation produced a reliable dental ceramic by SLA, with the shortest general manufacturing time and the highest mechanical strength when the layers were perpendicular to the test load surface.